When a chiral compound is used as a drug, an agricultural chemical, a fragance, or the like, there may be a case where only one of the enantiomers of the chiral compound exhibits the intended effect, or causes a side effect. Therefore, it is very important to determine the absolute configuration of a compound that is used as a drug, an agricultural chemical, a fragrance, or the like, or a raw material compound that is used to produce such a compound.
A method that utilizes circular dichroic spectroscopy and a method that utilizes nuclear magnetic resonance spectroscopy are known as a method for determining the absolute configuration of a chiral compound.
For example, Patent Literature 1 discloses a method that determines the absolute configuration of a chiral compound having a basic group that can be coordinated to a metal ion by coordinating the basic group to a metal ion of a metalloporphyrin having a specific structure, and measuring the circular dichroic spectrum of the product.
Patent Literature 2 discloses a method that determines the absolute configuration of an optically active alcohol by reacting a carboxyl group-containing optically active compound having a specific structure with an optically active alcohol or the like, and measuring the nuclear magnetic resonance spectrum of the resulting ester derivative or the like.
However the methods disclosed in Patent Literature 1 and 2 can only be applied to a chiral compound having a specific structure (coordinating atom or reactive group) from which a compound suitable for measurement can be derived.
A heavy atom method that utilizes the anomalous dispersion effect due to a heavy atom when implementing X-ray crystal structure analysis, and a method that introduces a chiral auxiliary (of which the absolute configuration is known) into the molecule of as chiral compound through an ionic bond or a covalent bond, and determines the absolute configuration of the chiral compound from the relative positional relationship with the chiral auxiliary, are known as a method for determining the absolute configuration of a chiral compound.
However, known X-ray crystal structure analysis has the following problems.
Specifically, it is necessary to prepare a high-quality single crystal when implementing X-ray crystal structure analysis. In order to prepare a high-quality single crystal, it is necessary to repeat a number of experiments through trial and error so as to determine optimum crystallization conditions. Therefore, X-ray crystal structure analysis is not necessarily efficient for determining the absolute configuration of a chiral compound.
It is normally necessary to provide at least several milligrams of sample (specimen) when conducting studies With regard to the crystallization conditions. Therefore, it is practically impossible to determine the absolute configuration of a chiral compound using X-ray crystal structure analysis when only a trace amount of chiral compound is available.